Bay State drugmaker targets asbestos-linked cancer

Heather Von St. James, 45, remembers her father, a demolition worker, coming home covered in dust and dirt. Still, she'd hug him each night and, sometimes, put on his coat and shoes to play.

Thirty years later, she paid a price. At age 36, with a 3-month-old daughter, Von St. James was diagnosed with mesothelioma, a deadly, incurable cancer tied to asbestos exposure that can take decades to develop and often kills within months after symptoms appear. She was told her only chance to live was to have a lung removed.

She opted for surgery, and later learned she had excised the disease in time. "There a lot of people who don't," Von St. James, of St. Paul, Minnesota, said by telephone.

Last year, more than 107,000 people worldwide died from mesothelioma. Now, drugs developed by a wave of drugmakers, from tiny Verastem Inc. in Cambridge, Mass., to giant GlaxoSmithKline Plc in London, are bringing new hope that the deadly disease's silent march within the body may be slowed or stopped.

"This is not a curable cancer," said Dean Fennell, lead investigator in a trial studying Verastem's drug. "It's not a disease that can be wiped out completely by surgery as you see with lung cancer. Finding ways to stop that process or slow it down can have big implications for patient survival."

Mesothelioma, unlike lung cancer, mostly affects the cells covering the lungs, and can also strike tissues around the heart and abdominal organs. As with all cancers, doctors treat mesothelioma by cutting it out, or irradiating it, both of which can carry dangerous side effects.

Verastem, Glaxo

The drug being developed by Verastem is in late-stage human testing. Glaxo's compound is being tried in combination with another product in an early-stage study. Both target an enzyme involved in cell movement, allowing the cancer to spread.

The enzyme is overabundant in many tumors and is a hallmark of aggressive cancers that spread quickly. Patients with an inactive gene called Neurofibromatosis 2, or NF2, respond best to such drugs, and about half of mesothelioma patients have inactive NF2s.

Verastem has been granted orphan drug status in the U.S. and Europe for its product, VS-6063. That means it would have seven years of market exclusivity from the time of approval. If cleared for sale, the drug may generate $450 million by 2019, according to the average of four analysts' estimates compiled by Bloomberg.

Earliest Stage

The medicine, also known as defactinib, targets cancer at its earliest stage: cancer stem cells, which are thought to be the source of the cancer and often resist existing therapies. Mesothelioma cancer stem cells are particularly hardy in that they can survive chemotherapy, Fennell, who is chairman of thoracic medical oncology at the University of Leicester in England, said in an interview.

"The hope is we can suppress the cancer in such a way that it becomes a more chronic disease, rather than have a disease that's going to progress relentlessly and kill the patient," said Fennell, who doesn't have a financial stake in Verastem and isn't a paid consultant, according to the company.

While Verastem, which has a market value of about $215 million, is developing the drug on its own, it has an array of industry heavyweights providing guidance. Board members and advisers include former Genzyme Corp. Chief Executive Officer Henri Termeer; Eric Lander, a principal leader of the Human Genome Project; and Phillip Sharp, a Nobel laureate who helped establish the company now known as Biogen Idec Inc.

Controlling Ownership

"Controlling ownership of our products is key to value creation," said Robert Forrester, Verastem's chief executive officer. "As we pursue clinical development and possible commercialization, we want to make sure that we retain the potential for a significant return on the development investment we are making for our shareholders."

AstraZeneca Plc of London is testing tremelimumab, which it licensed from Pfizer Inc., in mesothelioma in a mid-stage trial. The treatment works differently from the other drugs in development in that it helps the immune system recognize and kill cancer cells.

Glaxo, the U.K.'s biggest drugmaker, plans to test GSK2256098 in combination with some of its other medicines to potentially make cancer treatments more effective, Carolyn Buser-Doepner, vice president for tumor signaling at the London- based company, said in an interview. In one early-stage trial, it will be paired up with Glaxo's Mekinist, which is approved for melanoma.

"The pre-clinical data are very encouraging," she said. "We're very excited about it."

Boehringer's Drug

Glaxo said it will continue developing the drug after selling most of its cancer medicines to Novartis AG for as much as $16 billion. Novartis will have the right to partner with Glaxo on the product.

A fourth drug, nintedanib from Germany's Boehringer Ingelheim GmbH, is in early-stage testing for mesothelioma, according to a spokesman. It works differently than the other two medicines, targeting three proteins involved in the formation of blood vessels that feed tumors.

While it's encouraging to see treatments being tested for mesothelioma, the kind of research most likely to yield improvements in care is that looking into the nature of the disease itself, said Noel Snell, director of research at the British Lung Foundation.

"It is shameful that this kind of fundamental research remains so drastically underfunded, and that the number of trials available for mesothelioma patients is still dwarfed so dramatically by the number available to other cancer patients," Snell said in a statement.

In the U.S., $8.8 million in government funding has gone to research the disease, according to the Mesothelioma Applied Research Foundation.

Miracle Fiber

Asbestos was commonly used in building materials such as insulation for years because it was cheap, abundant and heat- resistant. Considered a "miracle fiber," it has been the subject of lawsuits claiming losses and damages from asbestos- related illnesses.

While some countries have banned asbestos mining, it continues in Russia, China and India, and the World Health Organization estimates as many as 125 million people worldwide are exposed to asbestos either at work or in their homes.

Mesothelioma can lay dormant for as long as 50 years before spreading, which explains why rates have risen long after many countries have banned the substance.

New cases in the U.K., where asbestos was restricted starting in the 1980s and outlawed fully in 2006, were 2,125 in 2012 and are expected to peak in 2015. Rates have been stable in the U.S., hovering around 3,000 new cases a year since 2000 due to education efforts, though a complete ban was overturned in the courts. Canada, which was one of the world's largest asbestos exporters, closed its remaining mines in 2011.

Japan 'Tsunami'

In Japan, where asbestos has been banned since 2006, the government pays the full cost of treatment for related illnesses and rates are expected to rise until 2027. Ken Takahashi, the lead author and director of a World Health Organization occupational health group, warned that Asian governments must brace themselves for an "asbestos tsunami."

"In the early '70s, this was an incredibly rare disease," Fennell said. "Now my clinic is full of patients with mesothelioma. Because the rates are increasing, we have a real need now to identify effective treatment."

For survivors like Von St. James, who has trouble breathing during the Minnesota winter with her one remaining lung, a solution can't come fast enough. She volunteers to coach patients through the deadly cancer, and says it's hard to watch so many friends lose the battle.

"The survival rate is pitifully 4 percent, most people don't live past 15 or 18 months," she said. "If they can keep it under control, that's the first hope."